(1) Abstract of the Disclosure
This invention relates to drug delivery systems, and more particularly to collagen-based drug delivery system and process for producing same.
(2) Background of the Invention
Collagen is the major protein in animals. It has an extended history of use in the medical field primarily due to its ability to polymerize in vitro into strong fibers that can be fabricated into a number of forms. Collagen has been utilized for a variety of clinical purposes including wound treatment, hemostasis, and soft tissue augmentation. The other medical applications of collagen have been described in a recent book entitled "Biocompatibility; Interactions of Biological and Implantable Material", Volume 1, Polymers by F. H. Silver and C. J. Doillon, YCH Publishers, New York, New York, 1989.
Soluble collagen has been used as a subcutaneous implant for repairing dermatological defects such as acne scars, glabellar furrows, excision scars and other soft tissue defects. Klein, A. W. J. Acad. Derm 9:224-228 (1983); Knapp, T. R., Luck, E. and Daniels, J. R. J. Surg. Res 23:96-105 (1977); and Kaplan, E. N., Falces, E. and Toileth, H. Clinical Utilization of Injectable Collagen, Ann. Plast. Surg., 10:437-151 (1983). Although it appears that this implant is readily accepted, the repair of the defects is temporary and patients need additional treatment after 6 to 18 months. There were also a number of adverse tissue responses after utilization of soluble collagen. Castrow, F. F. and Kruil, E. A. Injectable Collagen Implant--Update, J. Am. Acad. Dermatol. 9:889-893 (1983). Labow, T. A., and Silvers, D. N Late Reactions at Zydern Skin Test Sites, Cutis 35:154-158 (1984) and Cohen, I. K. Peacock, E. E. and Chvapil, M. Editorial on Zyderm. Plas. Reconstr. Surg., 73:1 (1984).
Collagen has also been used in many forms as a wound dressing. The various forms of collagen wound dressings include collagen sponges, such as described in Artandl U.S. Pat. No. 3,157,524 and Berg et al U.S. Pat. No. 4, 320,201; and collagen/polymer film composites, such as described in McKnight et al, U.S. Pat. No. 3,800,792. However, many of these dressings are not satisfactory for the various types of full thickness wounds. Collagen films and sponges do not readily conform to varied wound shapes Further, some collagen wound dressings have poor fluid absorption properties and enhance the pooling of wound fluids.
The use of wound dressings comprised of Type I collagen have limited commercial success because of the difficulty of the physical form of the dressing. Sponge dressings are difficult to apply to deep wounds because they do not adhere well to curved surfaces. Collagen in particulate form adheres well to wounds because of its high surface areas but is difficult to apply as dry powder because of its high surface charge. In the form of thin films, fluid absorption properties of collagen lead to pooling of fluids.